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Xanthone analogues as potent modulators of intestinal P-glycoprotein

Title
Xanthone analogues as potent modulators of intestinal P-glycoprotein
Authors
Chae, Song WhaWoo, SangwookPark, Jung HyunKwon, YoungjooNa, YounghwaLee, Hwa Jeong
Ewha Authors
이화정권영주
SCOPUS Author ID
이화정scopus; 권영주scopus
Issue Date
2015
Journal Title
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
ISSN
0223-5234JCR Link1768-3254JCR Link
Citation
vol. 93, pp. 237 - 245
Keywords
P-glycoprotein inhibitorXanthone analoguePaclitaxelBioavailabilityXenograft
Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Intestinal P-glycoprotein (P-gp) is a limiting step for oral absorption of drugs. Therefore, P-gp inhibitors have been studied as enhancers of oral absorption of drugs that are P-gp substrates. We investigated the in vitro and in vivo P-gp inhibitory activity of synthesized xanthone analogues. With 3-(3-chloro-2-hydroxypropoxy)-1-hydroxy-9H-thioxanthen-9-one, compound 13, accumulation of daunomycin (DNM) increased 707% and efflux of DNM decreased 66% compared to DNM alone. Relative bioavailability (RB) of paclitaxel (PTX, 25 mg/kg) increased 2.5-fold after oral administration with 13 (5 mg/kg). In a xenograft animal model, oral administration of PTX (40 mg/kg) with 13 (10 mg/kg) significantly inhibited tumour growth and was more effective than intravenously administered PTX (10 mg/kg) alone. Therefore, the synthesized xanthone analogue 13 might have therapeutic benefits for oral absorption of P-gp substrate anticancer drugs. (C) 2015 Published by Elsevier Masson SAS.
DOI
10.1016/j.ejmech.2015.01.006
Appears in Collections:
약학대학 > 약학과 > Journal papers
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